Electrical signaling in living cells controls a wide variety of arguably important physiological processes such as feeling, thinking, and heartbeat. Electrophysiological signals are created by proteins known as ion channels, and modulating the behavior of ion channels will alter the processes they control. The goal of my research program is to develop modulators selective for ion channel subtypes, to more precisely alter electrophysiological signals and identify channel subunits that generate native currents. Establishing the molecular identity of voltage-gated potassium (Kv) channels has been a particularly challenging problem: mammalian channels arise from a family of more than 40 genes, and pore-forming subunits can assemble as heterotetramers. Despite substantial and enduring efforts, few modulators of Kv channel activity have been discovered that are highly selective between channel subtypes. This is perhaps due to a high degree of sequence conservation between subfamily members in functionally important transmembrane segments. Our research efforts seek to enhance the selectivity of channel modulators by covalent attachment to benign, yet well-targeted, biologics.